Police are today appealing for witnesses to the collision on Botany Lane at the junction with Gawthorpe Green Lane in the Lepton area at around 5.30pm yesterday.
A Fiat Punto Grande crashed with a Peugeot Partner panel van.
The 31-year-old driver of the Fiat received "serious head injuries", police said, and was taken to Leeds General Infirmary by an air ambulance.
The driver of the van received minor injuries and was taken to Huddersfield Royal Infirmary.
Any witnesses to the collision or its lead-up is asked to contact the non-emergency police number 101.